July 02, 2010

Recent Tibetan adaptation for high altitude

Mountain-dwelling Tibetans have genetically adapted to life at altitude in the past 3000 years – the fastest genetic change known to have occurred in humans.

Rasmus Nielsen at the University of California, Berkeley, and his colleagues looked at the DNA of people living in two villages at 4300 and 4600 metres above sea level in Tibet. At these heights, oxygen levels are about 40 per cent lower than at sea level and lowlanders experience hypoxia, which is associated with headaches, fatigue, smaller fetuses and more deaths in infancy.

Tibetans don't suffer from hypoxia, but it has been unclear why. Nielsen's team compared the DNA of 50 Tibetans with that of 40 Han Chinese people from Beijing and 200 people of European ancestry from Denmark, all of whom live at altitudes below 2000 metres.

By comparing the DNA of the three groups, the team identified the specific genetic differences between the Tibetan and Han populations, thought to have diverged around 2750 years ago.

Science Vol. 329. no. 5987, pp. 72 - 75DOI: 10.1126/science.1189406

Genetic Evidence for High-Altitude Adaptation in Tibet

Tatum S. Simonson et al.

Abstract

Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP’s association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.

The 3000 years ago date appears to be a mutation rate date, and hence, subject to error bars that are huge relevant to the pre-history and early historical dates that matter to people trying to get the story of East Asian origins straight.

The overall similarity of Han and Tibetan genomes in non-adaptive traits supports the linguistic and archeological indications of the relatively recent common origins of the groups.

More relevant that the estimated date itself is the sequencing of the split that it implies. This study shows that the Han broke off from the Tibetans before the Tibetans made selective adaptations to high altitude. Genetic drift out of a high near current Tibetan population levels frequency of a no longer necessary high altitude oxygen processing allele would not have happened fast enough for it to be as rare as it is now in the Han Chinese population.

Thus, rather than being a Tibeto-Burmese urheimat, as an examination of linguistic diversity might suggest, Tibet looks more like a mountain refugia from a true homeland for the language family. This would put a Tibeto-Burman linguistic homeland not in the headwaters of the Yellow River, but further downstream, at Lanzhou or further East.

Since it is fair to guess, selective pressure on proto-Tibetans to adapt to high altitude would have been early and intense. Babies born without these adaptations are far less likely to survive to have children of there own. Even if half a dozen generations, an adaptation of this extreme level of adaptive benefit would become dramatically more frequent. It would probably have taken hold more rapidly than lactose tolerance, for example.

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